The Properties of Lysergic Acid Diethylamide History
Lysergic acid diethylamide (LSD) was first synthesized by Dr. Albert Hofmann on November 16, 1938 [10]. At the time, it was determined to have no interesting pharmacological effects but on April 16, 1943, Dr. Hofmann decided on a hunch to synthesize the compound again and accidentally ingested a portion, expectedly during recrystallization, and underwent a change in his state of consciousness [10]. On April 19, Dr. Hofmann intentionally ingested the compound and confirmed its psychedelic properties [10]. In 1947, Sandoz Laboratories began marketing LSD as a psychiatric cure-all under the name “Delysid” and it was prescribed to over 40,000 patients between 1950 and 1965 [7].
As medical professionals became familiar with the drug, some began to use it themselves and it gained popularity among academics [7]. In the late 1960s, LSD became intertwined with the counterculture of the period. Student protestors started a “psychedelic movement” within the Vietnam War protests, which created a backlash that greatly contributed to the outlaw of the drug [17]. The FDA classified LSD as an investigational new drug and many states began to outlaw LSD and publish anti-LSD warnings, which actually resulted in an increase in the interest and availability of LSD [4]. The relative ease with which LSD could be produced and its extremely small dosage size (which is measured in micrograms) allowed black market producers to easily exceed the quickly-growing demand for the drug [4].
Description
Lysergic acid, which is a precursor to LSD, is naturally produced by the rye fungus C. purpurea and can be converted to LSD by reaction with diethylamine [17]. LSD is a colorless, odorless, tasteless crystalline solid [4]. It has a molecular weight of 323.42 g/mol (chemical formula C20H25ON3) and melts at 83°C [17]. There are two stereocenters in LSD, and it exists as the isomers d- and l-lysergic acid diethylamide and d- and l-isolysergic acid diethylamide, but only d-LSD is psychoactive [17]. LSD is stable as a solid, but in a basic solution it will interchange with its iso-LSD isomer and in the presence of water or alcohol, light will catalyze a reaction to form lumi-LSD, which is the result of addition to the double bond between the 8-position carbon and the aromatic ring [20].
Psychological Effects
Subjects administered a moderate dose of LSD (75 to 150 micrograms) generally enter one of three altered states of consciousness: a moderately euphoric state (which is most common), a dysphoric state, or an ambivalent state [13] [17]. Subjects in the euphoric state appear happy, view others as friendly, and have some feelings of jitteriness but do not fear losing control of themselves [13]. Subjects in the dysphoric state are dominated by feelings of fear, depression, and tension and have impaired cognition [13]. Subjects in the ambivalent state appear to be in the happiest of the three states, but report intense conflicting emotions, feeling both relaxed and jittery, viewing others as both friendly and suspicious, and feeling safe yet out of control [13]. Most subjects’ experiences share characteristics from all three states, having strong opposing emotions occur simultaneously, a lack of control of emotions and thoughts, dissociation from the real world, an increase in perception (but having unreal perceptions), and a sense of friendliness and suspiciousness about others [13]. The effects may also include visual hallucinations including radiant colors, surfaces appearing to ripple, familiar objects appearing strange, synesthesia, geometric shapes behind closed eyes, stretching of time, and lingering after-images [18].
Cognitive Effects
While under the effects of LSD, subjects have decreased cognitive ability. Coordination, reaction time, attention, concentration, intellectual functions, and memory are all impaired by LSD although learning processes are unaffected and impaired performance on arithmetic occurs only in doses above 50 micrograms [17]. There are no lasting cognitive impairments following exposure [17].
Physiological Effects
LSD is not addictive as its use does not result in a dopamine release, which seems to be the basis of addiction, but instead affects the 5-HT2A receptors and invokes a glutamate release [15]. By studying LSD in rats, it was determined that the drug directly stimulates 5-HT receptors, resulting in its pharmacological effects [2]. After two to three days of consistent use, subjects develop a reduction of 5-HT2A receptor density, which results in a tolerance to the effects of LSD that will last several days until receptor density returns to normal [8] [17].
The presence of LSD in human plasma when administered intravenously was determined by fluorimetry and found to have a half-life of 175 minutes [1]. Subjects were given tests consisting of simple addition problems after each blood sample was taken and it was found that test scores increased as LSD concentration decreased, with test scores approaching normal as LSD concentration approached zero [1]. However, the presence of LSD in human plasma when administered orally was determined by gas chromatography – mass spectrometry and found to have a half-life of 5.1 hours [16].
Somatic Effects
LSD activates the sympathetic nervous system, as indicated by a dilation of the pupils, a slight increase in heart rate, increase in blood pressure, and occasionally an increase in blood-sugar levels and body temperature [17]. Other common symptoms are sweating, salivation, occasionally nausea or vomiting, and flushing of the face, which all indicate stimulation of the parasympathetic nervous system [17]. Although the effects vary between individuals, the sympathetic response is almost always predominates [17].
Toxicology
The LD50 of LSD in different species varies greatly, from 0.3mg/kg i.v. in rabbits to 60mg/kg i.v. in mice [17]. The LD50 in humans is unknown, as there have been no documented cases of death from LSD overdose; even eight individuals who mistook LSD for cocaine and ingested enough LSD to achieve plasma concentrations of up to 70mg/L survived with hospital treatment and had no lasting effects [17].
Uses
Early studies of the medical potential of LSD-assisted psychotherapy suggested LSD could be used to treat end-of-life anxiety, alcoholism, and the symptoms of psychiatric illnesses [5]. LSD-assisted psychotherapy was studied with advanced-stage cancer patients and was shown to alleviate symptoms of anxiety, tension, depression, sleep disturbances, psychological withdrawal, and physical pain [5]. It is suspected that LSD helps to relieve pain by reducing the subject’s ability to concentrate on a single sensory input, such as pain, and by making other sensations seem more important, even those not vital to survival [12]. When administered to terminally ill patients as an analgesic, LSD seems to decrease the perception in the patient of their pain being inescapable and reduce their ability to anticipate death, in turn reducing anxiety even up to a week after treatment [12]. In Switzerland in 2008, Dr. Peter Gasser received government approval to research LSD in humans (for the first time since 1972) and completed a study on how LSD affects anxiety from life-threatening illnesses with “promising (preliminary) results” [5].
When used during psychosocial interventions, a single dose of LSD has been shown to significantly improve the results of alcoholism treatment in the first six months (which is rare for a psychiatric drug to have positive effects for such a long period following a single dose), but the number of subjects who maintained abstinence from alcohol after twelve months was not statistically significant when compared to the control group [14]. When used similarly to treat heroin addiction, a single dose of LSD resulted in a significantly lower rate of relapse even after twelve months following treatment [14]. Research on repeated doses of LSD used during treatment is unavailable, but such a treatment regimen may have sustained results [14].
LSD use has also been shown to increase creativity. In one study, several artists were asked to draw and paint a Kachina doll both while sober and while under the effects of LSD [11]. The renderings under the effects of LSD contained many changes, including “relative size expansion; involution; movement; alteration of figure/ground and boundaries; greater intensity of color and light; oversimplification; symbolic and abstract depiction of objects; and fragmentation, disorganization, and distortion” and were generally viewed by the artists to be more interesting and aesthetically superior [11].
Adverse Effects
The most common adverse effect of LSD is an episode of anxiety, panic, or paranoid thoughts while under the influence of the drug, which may temporarily result in depressive mood swings or psychic instability following the experience [17]. In some rare cases, subjects can spontaneously experience flashbacks, or recurrences of some or all of their hallucinogenic symptoms, in the weeks or months (or even more rarely, years) following a particularly traumatic episode [17] [9]. Subjects with existing mental illnesses can rarely experience prolonged psychotic episodes as an effect of LSD [6].
LSD can interact with some medications, most notably antidepressants. Lithium and tricyclic antidepressants typically intensify the effect of LSD and sometimes cause a dissociative fugue state while SSRIs and MAOIs generally decrease the effects of LSD, probably because they affect the 5-HT2A receptors and 5-HT concentrations [3].
Detection
LSD is rapidly metabolized in humans to several structurally similar metabolites, the most dominant of which in urine is 2-oxy-3-hydroxy-LSD [17]. LSD is detectable in urine for about 4 days following ingestion, with its metabolites detectable only for a slightly longer period of time [17]. Using an LSD ImmunEluteTM chromatographic column designed specifically to purify samples for LSD detection by utilizing a resin containing monoclonal antibodies to LSD, a detection limit of <50pg can be achieved [19]. Although the column was intended for detection of LSD in urine, the detection of LSD in serum was not significantly different [19]. The detection of LSD in hair samples, however, is more difficult. In one study, hair samples from nine volunteers who reported using LSD were analyzed but LSD could only be detected in one sample at a concentration of 1pg/mg for 112mg of hair, indicating that LSD has a very low detectability in hair due to its low dosage [19].
References
1. Aghajanian, G. K. and Bing, O. H. L. (1964). "Persistence of Lysergic Acid Diethylamide in the Plasma of Human Subjects". Clin.Pharmacol.Ther.. Vol. 5, 611-614. http://www.maps.org/w3pb/new/1964/1964_aghajanian_2224_1.pdf. Retrieved 7 Dec. 2012.
2. Andén, N. E., Corrodi, H., Fuxe K., and Hökfelt, T. (1968). "Evidence for a Central 5-Hydroxytryptamine Receptor Stimulation by Lyserfic Acid Diethylamide". Br. J. Pharmac.. Vol 34, 1-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1703426/pdf/brjpharm00576-0007.pdf Retreived 7 Dec 2012.
3. Bonson, K. R., Buckholtz, J. W., and Murphy, D. L. (1996). "Chronic Administration of Serotonergic Antidepressants Attenuates the Subjective Effects of LSD in Humans". Neuropsychopharmacology. Vol. 14, 425-436. doi:10.1016/0893-133X(95)00145-4
4. Brecher, E. M. (1972). "How LSD Was Popularized, 1962-1969". The Consumers Union Report on Licit and Illicit Drugs. http://www.druglibrary.org/schaffer/Library/studies/cu/CU50.html. Retrieved 7 Dec 2012.
5. Brown, D. J. (2011). "Landmark Clinical LSD Study Nears Completion". Santa Cruz Patch. http://santacruz.patch.com/articles/landmark-clinical-lsd-study-nears-completion. Retrieved 8 Dec 2012.
6. Cohen, S. (1960). "Lysergic Acid Diethylamide: Side Effects and Complications". Journal of Nervous and Mental Disease. Vol. 130(1), 30-40. doi:10.1097/00005053-196001000-00005
7. DEA Public Affairs (2001-11-16). "LSD: The Drug". http://web.petabox.bibalex.org/web/20011116091659/www.usdoj.gov/dea/pubs/lsd/lsd-4.htm. Retrieved 7 Dec 2012.
8. Gresch, P. J., Smith, R. L., Barrett, R. J., and Sanders-Bush, E. (2005). "Behavioral Tolerance to Lysergic Acid Diethylamide is Associated with Reduced Serotonin-2A Receptor Signaling in Rat Cortex". Neuropsychopharmacology. Vol. 30, 1693-1702. doi:10.1038/sj.npp.1300711
9. Halpern, J. H. and Pope, H. G. Jr (2003). "Hallucinogen Persisting Perception Disorder: What Do We Know After 50 Years?". Drug and Alcohol Dependence. Vol. 69(2), 109-119. doi:10.1016/S0376-8716(02)00306-x
10. Hofmann, A. (1996). "LSD: Completely Personal". Worlds of Consciousness Conference. http://www.maps.org/news-letters/v06n3/06346hof.html. Retrieved 7 Dec 2012.
11. Janiger, O. and Dobkin de Rios, M. (1989). "LSD and Creativity". Journal of Psychoactive Drugs. Vol. 21(1) 129-134. doi:10.1080/02791072.1989.10472150
12. Kast, E. (1967). "Attenuation of Anticipation: A Therapeutic Use of Lysergic Acid Diethylamide". Psychiat.Quart.. Vol. 41, 646-657. doi:10.1007/BF01575629
13. Katz, M. M. and Waskow, I. E. (1968). "Characterizing the Psychological State Produced by LSD". Journal of Abnormal Psychology. Vol 73(1), 1-14. doi:10.1037/h0020114 url:http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=5639999.ui. Retrieved 7 Dec 2012.
14. Krebs, T. S. and Johansen, Pål-Ørjan (2012). "Lysergic Acid Diethylamide (LSD) for Alcoholism: Meta-Analysis of Randomized Controlled Trials". Journal of Psychopharmacology. doi:10.1177/0269881112439253
15. Lüscher C. and Ungless M. A. (2006). "The Mechanistic Classification of Addictive Drugs". PLoS Med 3(11): e437. doi:10.1371/journal.pmed.0030437
16. Papac, D. I. and Foltz, R. L. (1990). "Measurement of Lysergic Acid Diethylamide (LSD) in Human Plasma by Gas Chromatography/Negative Ion Chemical Ionization Mass Spectrometry". Journal of Analytical Technology. Vol 14, 189-190. http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=6265&DocPartID=6624. Retrieved 7 Dec 2012.
17. Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M. and Hintzen, A. (2008). "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, 14: 295–314. doi:10.1111/j.1755-5949.2008.00059.x
18. "Psychedelic Effects". TheGoodDrugsGuide.com. http://www.thegooddrugsguide.com/lsd/psychedelic.htm. Retrieved 7 Dec 2012.
19. Röhrich, J.,Zörntlein, S., Becker, J. (2000). "Analysis of LSD in Human Body Fluids and Hair Samples Applying ImmunElute Columns". Forensic Science International. Vol. 107(1–3), 181-190. doi:10.1016/S0379-0738(99)00162-0
20. Shulgin, A. and Shulgin, A. (1997). "LSD". TiHKAL. http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml. Retrieved 8 Dec 2012.
History
Lysergic acid diethylamide (LSD) was first synthesized by Dr. Albert Hofmann on November 16, 1938 [10]. At the time, it was determined to have no interesting pharmacological effects but on April 16, 1943, Dr. Hofmann decided on a hunch to synthesize the compound again and accidentally ingested a portion, expectedly during recrystallization, and underwent a change in his state of consciousness [10]. On April 19, Dr. Hofmann intentionally ingested the compound and confirmed its psychedelic properties [10]. In 1947, Sandoz Laboratories began marketing LSD as a psychiatric cure-all under the name “Delysid” and it was prescribed to over 40,000 patients between 1950 and 1965 [7].
As medical professionals became familiar with the drug, some began to use it themselves and it gained popularity among academics [7]. In the late 1960s, LSD became intertwined with the counterculture of the period. Student protestors started a “psychedelic movement” within the Vietnam War protests, which created a backlash that greatly contributed to the outlaw of the drug [17]. The FDA classified LSD as an investigational new drug and many states began to outlaw LSD and publish anti-LSD warnings, which actually resulted in an increase in the interest and availability of LSD [4]. The relative ease with which LSD could be produced and its extremely small dosage size (which is measured in micrograms) allowed black market producers to easily exceed the quickly-growing demand for the drug [4].
Description
Lysergic acid, which is a precursor to LSD, is naturally produced by the rye fungus C. purpurea and can be converted to LSD by reaction with diethylamine [17]. LSD is a colorless, odorless, tasteless crystalline solid [4]. It has a molecular weight of 323.42 g/mol (chemical formula C20H25ON3) and melts at 83°C [17]. There are two stereocenters in LSD, and it exists as the isomers d- and l-lysergic acid diethylamide and d- and l-isolysergic acid diethylamide, but only d-LSD is psychoactive [17]. LSD is stable as a solid, but in a basic solution it will interchange with its iso-LSD isomer and in the presence of water or alcohol, light will catalyze a reaction to form lumi-LSD, which is the result of addition to the double bond between the 8-position carbon and the aromatic ring [20].
Psychological Effects
Subjects administered a moderate dose of LSD (75 to 150 micrograms) generally enter one of three altered states of consciousness: a moderately euphoric state (which is most common), a dysphoric state, or an ambivalent state [13] [17]. Subjects in the euphoric state appear happy, view others as friendly, and have some feelings of jitteriness but do not fear losing control of themselves [13]. Subjects in the dysphoric state are dominated by feelings of fear, depression, and tension and have impaired cognition [13]. Subjects in the ambivalent state appear to be in the happiest of the three states, but report intense conflicting emotions, feeling both relaxed and jittery, viewing others as both friendly and suspicious, and feeling safe yet out of control [13]. Most subjects’ experiences share characteristics from all three states, having strong opposing emotions occur simultaneously, a lack of control of emotions and thoughts, dissociation from the real world, an increase in perception (but having unreal perceptions), and a sense of friendliness and suspiciousness about others [13]. The effects may also include visual hallucinations including radiant colors, surfaces appearing to ripple, familiar objects appearing strange, synesthesia, geometric shapes behind closed eyes, stretching of time, and lingering after-images [18].
Cognitive Effects
While under the effects of LSD, subjects have decreased cognitive ability. Coordination, reaction time, attention, concentration, intellectual functions, and memory are all impaired by LSD although learning processes are unaffected and impaired performance on arithmetic occurs only in doses above 50 micrograms [17]. There are no lasting cognitive impairments following exposure [17].
Physiological Effects
LSD is not addictive as its use does not result in a dopamine release, which seems to be the basis of addiction, but instead affects the 5-HT2A receptors and invokes a glutamate release [15]. By studying LSD in rats, it was determined that the drug directly stimulates 5-HT receptors, resulting in its pharmacological effects [2]. After two to three days of consistent use, subjects develop a reduction of 5-HT2A receptor density, which results in a tolerance to the effects of LSD that will last several days until receptor density returns to normal [8] [17].
The presence of LSD in human plasma when administered intravenously was determined by fluorimetry and found to have a half-life of 175 minutes [1]. Subjects were given tests consisting of simple addition problems after each blood sample was taken and it was found that test scores increased as LSD concentration decreased, with test scores approaching normal as LSD concentration approached zero [1]. However, the presence of LSD in human plasma when administered orally was determined by gas chromatography – mass spectrometry and found to have a half-life of 5.1 hours [16].
Somatic Effects
LSD activates the sympathetic nervous system, as indicated by a dilation of the pupils, a slight increase in heart rate, increase in blood pressure, and occasionally an increase in blood-sugar levels and body temperature [17]. Other common symptoms are sweating, salivation, occasionally nausea or vomiting, and flushing of the face, which all indicate stimulation of the parasympathetic nervous system [17]. Although the effects vary between individuals, the sympathetic response is almost always predominates [17].
Toxicology
The LD50 of LSD in different species varies greatly, from 0.3mg/kg i.v. in rabbits to 60mg/kg i.v. in mice [17]. The LD50 in humans is unknown, as there have been no documented cases of death from LSD overdose; even eight individuals who mistook LSD for cocaine and ingested enough LSD to achieve plasma concentrations of up to 70mg/L survived with hospital treatment and had no lasting effects [17].
Uses
Early studies of the medical potential of LSD-assisted psychotherapy suggested LSD could be used to treat end-of-life anxiety, alcoholism, and the symptoms of psychiatric illnesses [5]. LSD-assisted psychotherapy was studied with advanced-stage cancer patients and was shown to alleviate symptoms of anxiety, tension, depression, sleep disturbances, psychological withdrawal, and physical pain [5]. It is suspected that LSD helps to relieve pain by reducing the subject’s ability to concentrate on a single sensory input, such as pain, and by making other sensations seem more important, even those not vital to survival [12]. When administered to terminally ill patients as an analgesic, LSD seems to decrease the perception in the patient of their pain being inescapable and reduce their ability to anticipate death, in turn reducing anxiety even up to a week after treatment [12]. In Switzerland in 2008, Dr. Peter Gasser received government approval to research LSD in humans (for the first time since 1972) and completed a study on how LSD affects anxiety from life-threatening illnesses with “promising (preliminary) results” [5].
When used during psychosocial interventions, a single dose of LSD has been shown to significantly improve the results of alcoholism treatment in the first six months (which is rare for a psychiatric drug to have positive effects for such a long period following a single dose), but the number of subjects who maintained abstinence from alcohol after twelve months was not statistically significant when compared to the control group [14]. When used similarly to treat heroin addiction, a single dose of LSD resulted in a significantly lower rate of relapse even after twelve months following treatment [14]. Research on repeated doses of LSD used during treatment is unavailable, but such a treatment regimen may have sustained results [14].
LSD use has also been shown to increase creativity. In one study, several artists were asked to draw and paint a Kachina doll both while sober and while under the effects of LSD [11]. The renderings under the effects of LSD contained many changes, including “relative size expansion; involution; movement; alteration of figure/ground and boundaries; greater intensity of color and light; oversimplification; symbolic and abstract depiction of objects; and fragmentation, disorganization, and distortion” and were generally viewed by the artists to be more interesting and aesthetically superior [11].
Adverse Effects
The most common adverse effect of LSD is an episode of anxiety, panic, or paranoid thoughts while under the influence of the drug, which may temporarily result in depressive mood swings or psychic instability following the experience [17]. In some rare cases, subjects can spontaneously experience flashbacks, or recurrences of some or all of their hallucinogenic symptoms, in the weeks or months (or even more rarely, years) following a particularly traumatic episode [17] [9]. Subjects with existing mental illnesses can rarely experience prolonged psychotic episodes as an effect of LSD [6].
LSD can interact with some medications, most notably antidepressants. Lithium and tricyclic antidepressants typically intensify the effect of LSD and sometimes cause a dissociative fugue state while SSRIs and MAOIs generally decrease the effects of LSD, probably because they affect the 5-HT2A receptors and 5-HT concentrations [3].
Detection
LSD is rapidly metabolized in humans to several structurally similar metabolites, the most dominant of which in urine is 2-oxy-3-hydroxy-LSD [17]. LSD is detectable in urine for about 4 days following ingestion, with its metabolites detectable only for a slightly longer period of time [17]. Using an LSD ImmunEluteTM chromatographic column designed specifically to purify samples for LSD detection by utilizing a resin containing monoclonal antibodies to LSD, a detection limit of <50pg can be achieved [19]. Although the column was intended for detection of LSD in urine, the detection of LSD in serum was not significantly different [19]. The detection of LSD in hair samples, however, is more difficult. In one study, hair samples from nine volunteers who reported using LSD were analyzed but LSD could only be detected in one sample at a concentration of 1pg/mg for 112mg of hair, indicating that LSD has a very low detectability in hair due to its low dosage [19].
References
1. Aghajanian, G. K. and Bing, O. H. L. (1964). "Persistence of Lysergic Acid Diethylamide in the Plasma of Human Subjects". Clin.Pharmacol.Ther.. Vol. 5, 611-614. http://www.maps.org/w3pb/new/1964/1964_aghajanian_2224_1.pdf. Retrieved 7 Dec. 2012.
2. Andén, N. E., Corrodi, H., Fuxe K., and Hökfelt, T. (1968). "Evidence for a Central 5-Hydroxytryptamine Receptor Stimulation by Lyserfic Acid Diethylamide". Br. J. Pharmac.. Vol 34, 1-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1703426/pdf/brjpharm00576-0007.pdf Retreived 7 Dec 2012.
3. Bonson, K. R., Buckholtz, J. W., and Murphy, D. L. (1996). "Chronic Administration of Serotonergic Antidepressants Attenuates the Subjective Effects of LSD in Humans". Neuropsychopharmacology. Vol. 14, 425-436. doi:10.1016/0893-133X(95)00145-4
4. Brecher, E. M. (1972). "How LSD Was Popularized, 1962-1969". The Consumers Union Report on Licit and Illicit Drugs. http://www.druglibrary.org/schaffer/Library/studies/cu/CU50.html. Retrieved 7 Dec 2012.
5. Brown, D. J. (2011). "Landmark Clinical LSD Study Nears Completion". Santa Cruz Patch. http://santacruz.patch.com/articles/landmark-clinical-lsd-study-nears-completion. Retrieved 8 Dec 2012.
6. Cohen, S. (1960). "Lysergic Acid Diethylamide: Side Effects and Complications". Journal of Nervous and Mental Disease. Vol. 130(1), 30-40. doi:10.1097/00005053-196001000-00005
7. DEA Public Affairs (2001-11-16). "LSD: The Drug". http://web.petabox.bibalex.org/web/20011116091659/www.usdoj.gov/dea/pubs/lsd/lsd-4.htm. Retrieved 7 Dec 2012.
8. Gresch, P. J., Smith, R. L., Barrett, R. J., and Sanders-Bush, E. (2005). "Behavioral Tolerance to Lysergic Acid Diethylamide is Associated with Reduced Serotonin-2A Receptor Signaling in Rat Cortex". Neuropsychopharmacology. Vol. 30, 1693-1702. doi:10.1038/sj.npp.1300711
9. Halpern, J. H. and Pope, H. G. Jr (2003). "Hallucinogen Persisting Perception Disorder: What Do We Know After 50 Years?". Drug and Alcohol Dependence. Vol. 69(2), 109-119. doi:10.1016/S0376-8716(02)00306-x
10. Hofmann, A. (1996). "LSD: Completely Personal". Worlds of Consciousness Conference. http://www.maps.org/news-letters/v06n3/06346hof.html. Retrieved 7 Dec 2012.
11. Janiger, O. and Dobkin de Rios, M. (1989). "LSD and Creativity". Journal of Psychoactive Drugs. Vol. 21(1) 129-134. doi:10.1080/02791072.1989.10472150
12. Kast, E. (1967). "Attenuation of Anticipation: A Therapeutic Use of Lysergic Acid Diethylamide". Psychiat.Quart.. Vol. 41, 646-657. doi:10.1007/BF01575629
13. Katz, M. M. and Waskow, I. E. (1968). "Characterizing the Psychological State Produced by LSD". Journal of Abnormal Psychology. Vol 73(1), 1-14. doi:10.1037/h0020114 url:http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=5639999.ui. Retrieved 7 Dec 2012.
14. Krebs, T. S. and Johansen, Pål-Ørjan (2012). "Lysergic Acid Diethylamide (LSD) for Alcoholism: Meta-Analysis of Randomized Controlled Trials". Journal of Psychopharmacology. doi:10.1177/0269881112439253
15. Lüscher C. and Ungless M. A. (2006). "The Mechanistic Classification of Addictive Drugs". PLoS Med 3(11): e437. doi:10.1371/journal.pmed.0030437
16. Papac, D. I. and Foltz, R. L. (1990). "Measurement of Lysergic Acid Diethylamide (LSD) in Human Plasma by Gas Chromatography/Negative Ion Chemical Ionization Mass Spectrometry". Journal of Analytical Technology. Vol 14, 189-190. http://www.erowid.org/references/refs_view.php?A=ShowDocPartFrame&C=ref&ID=6265&DocPartID=6624. Retrieved 7 Dec 2012.
17. Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M. and Hintzen, A. (2008). "The Pharmacology of Lysergic Acid Diethylamide: A Review". CNS Neuroscience & Therapeutics, 14: 295–314. doi:10.1111/j.1755-5949.2008.00059.x
18. "Psychedelic Effects". TheGoodDrugsGuide.com. http://www.thegooddrugsguide.com/lsd/psychedelic.htm. Retrieved 7 Dec 2012.
19. Röhrich, J.,Zörntlein, S., Becker, J. (2000). "Analysis of LSD in Human Body Fluids and Hair Samples Applying ImmunElute Columns". Forensic Science International. Vol. 107(1–3), 181-190. doi:10.1016/S0379-0738(99)00162-0
20. Shulgin, A. and Shulgin, A. (1997). "LSD". TiHKAL. http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml. Retrieved 8 Dec 2012.